EGFR+ Progression (T790M Negative) - Treatment Options - 1291245

dlhp2010
Posts:1

Hello Grace:

It has been a while since I have posted, but I am sad to report that we lost my wife (Maria) in June to her nearly 7 year battle with stage IV NSCLC. I can not say enough good things about the inspiring care she received from Dr. Hensing and his Team at the Northshore University Health System near Chicago and Dr. Sequist at Massachusetts General Hospital in Boston, not to mention the support and guidance we received from GRACE. Everyone was tremendous and so giving for those of us in this universe. In Maria's case, she was diagnosed at stage IV with multiple sites of spread in 2010. Yet, she beat the illness for a long time, thanks in large part to a 5 year, 3 month response to Tarceva. Our son actually thanked Genentech at her memorial service.

Now, I have a new question regarding my wife's brother in Mexico, who was also diagnosed with EGFR+ (Exon 19 del) stage IV NSCLC about 3 three years ago (with brain mets). He had a two year stint on Afatinib, and after progression (he is T790M negative) has relied on radiation and now a combination of Carboplatin and Pemetrexed to fight the disease. His Foundation One report just came in and I'm wondering if the Grace Team has any treatment thoughts based on their clinical experience re: the mutations that were identified, as follows (we are of course reviewing in detail the treatment suggestions provided in the report):

Alterations Identified:

EGFR exon 19 del (E746_A750del)
PIK3CA E545K
CREBBP truncation exon 31
RB1 truncation exon 9
TP53 R248W

Additional Findings:

Microsatelite Status: MS-Stable
Tumor Mutation Burden TMB-Low; 4 Muts/Mb

No Reportable Alterations Identified:

KRAS
ALK
BRAF
MET
RET
ERBB2
ROS1

Thank You for any thoughts you may have!

Dan

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JimC
Posts: 2753

Hello Dan,

I am so very sorry to hear of the loss of your dear wife to this cruel disease. She was indeed fortunate to have your steadfast support as well as that of Dr. Hensing, who as you know was my late wife's oncologist as well and about whom I can never say enough. And you have been a good friend to GRACE over the years.

And I'm saddened to hear that Maria's brother has been diagnosed as well. In answer to a similar question, Dr. West stated:

"There is certainly no established treatment for a lung cancer with a PIK3CA alteration, but trials are trying to look into this. Perhaps most promising would be the ASCO TAPUR trial (www.tapur.org) trial that is just launching and will be widely available at many centers across the US and perhaps beyond it, enabling patients with various different uncommon mutations to try novel targeted therapy options all as part of one large trial effort. The trial may not be available at your center but is going to be opening in many places in the next few months.

I believe the NCI-MATCH trial would potentially serve a similar function, though I believe it requires that patients submit tissue specifically as part of the trial, rather than use outside results. That trial is also on hold right now, and I’m not sure of the time line for it re-opening.

Finally, though it isn’t a molecularly targeted therapy, Taxotere (docetaxel)-based chemo, with or without Cyramza (ramicirumab), has been FDA approved and has an established survival benefit in patients with advanced NSCLC who have received prior chemo." - http://cancergrace.org/topic/looking-for-a-new-plan-b#post-1273227

I don't have any information on the other detected mutations, although he might want to keep an eye on clinicaltrials.gov, searching for each of those mutations. For example, there is a trial dealing with TP53 and various cancers, including lung cancer: https://clinicaltrials.gov/ct2/show/NCT02432963?term=TP53&recrs=a&cond=…

[continued}

JimC
Posts: 2753

[continued]

Another possibility might be immunotherapy, although EGFR+ patients tend to have lower response rates to the checkpoint inhibitors.

I am so glad that LIsa and I had a chance to meet you at the GRACE receptions. Our thoughts are with you for peace and comfort.

JimC
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